High-dose chemotherapy with autologous stem cell rescue followed by posterior fossa irradiation for local medulloblastoma recurrence or progression after conventional chemotherapy

Cancer. 2007 Jul 1;110(1):156-63. doi: 10.1002/cncr.22761.

Abstract

Background: The objective of the current study was to determine the outcome of children with local recurrence or progression of medulloblastoma in patients who received high-dose chemotherapy (HDC) and posterior fossa (PF) irradiation.

Methods: HDC consisted in busulfan at a dose of 600 mg/m(2) and thiotepa at a dose of 900 mg/m(2) followed by autologous stem cells transplantation (ASCT). PF radiotherapy was delivered at doses from 50 grays (Gy) to 55 Gy on Day +70 after ASCT. Twenty-seven patients developed local recurrence of an initially completely resected medulloblastoma. Twelve patients had local residual disease after surgery and were enrolled into the salvage protocol at the time of local disease progression under conventional chemotherapy.

Results: Acute toxicity consisted mainly in hepatic veno-occlusive disease (33% of patients) and bone marrow aplasia. Two toxic deaths (5%) from infections were reported. The 5-year overall survival rate after this salvage treatment (OS(5y)) for the 39 children who were treated was 68.8% (95% confidence interval [95% CI], 53-81.2%). In the group of patients who were treated for local recurrence, the OS(5y) was 77.2% (95% CI, 58.3-89.1%). Patients with local residual disease who were treated at the time of disease progression had an OS(5y) after salvage treatment of only 50% (95% CI, 25.4-74.6%; P = .09).

Conclusions: The treatment strategy that was used in this study had manageable immediate toxicity and resulted in a high overall survival rate in the setting of young children with medulloblastoma who developed local recurrence or disease progression.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Aspergillosis / etiology
  • Busulfan / administration & dosage
  • Busulfan / adverse effects
  • Cerebellar Neoplasms / pathology
  • Cerebellar Neoplasms / therapy*
  • Child
  • Child, Preschool
  • Combined Modality Therapy
  • Cranial Irradiation / methods
  • Disease Progression
  • Dose-Response Relationship, Drug
  • Humans
  • Infant
  • Lung Diseases, Fungal / etiology
  • Medulloblastoma / pathology
  • Medulloblastoma / therapy*
  • Neoplasm Recurrence, Local
  • Neutropenia / etiology
  • Pneumonia / etiology
  • Radiotherapy, Conformal / methods
  • Salvage Therapy
  • Stem Cell Transplantation / adverse effects
  • Stem Cell Transplantation / methods*
  • Survival Analysis
  • Thiotepa / administration & dosage
  • Thiotepa / adverse effects
  • Treatment Outcome

Substances

  • Thiotepa
  • Busulfan